Prevalence and Etiologies of Non-Responsive Celiac Disease: A Systematic Review and Meta-Analysis

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Conference Proceeding

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Publication Title

American Journal of Gastroenterology


Introduction: Lifelong gluten free diet (GFD) is the only known treatment of celiac disease (CeD), but the response is variable and a significant proportion of patients may continue to experience clinical symptoms despite adherence to GFD. Non-responsive CeD (NRCD) is defined as lack of initial response to GFD in patients with CeD after 6-12 months of GFD, or recurrence of symptoms in a patient who initially responded to GFD despite continued dietary adherence. Recent studies have been inconsistent on the proportion of NRCD amongst patients with CeD. Therefore, we decided to conduct a systematic review and meta-analysis to determine the prevalence and causes of NRCD. Methods: We conducted a search of the PubMed, Embase and the Cochrane Library databases for original studies published in English reporting the proportion of patients with persistent symptoms after .6 months of GFD. Studies reporting the etiologies of NRCD were identified separately. The systematic review was conducted as per the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Quality assessment was performed using the Newcastle Ottawa Scale. Statistical analysis was performed in STATA v14. Results: Of a total of 792 search results, after inclusion and exclusion criteria, 8 studies were included in the systematic review, of which 5 studies (n5 4,414) reported data on the prevalence of NRCD and 6 studies (n5 678) reported the causes of NRCD. Pooled prevalence of NRCD was 22% (95%CI, 11-35%, I25 98.6%, Figure 1). Amongst patients with NRCD, inadvertent exposure to gluten was the most common cause (49% [95%CI, 36-63%, I25 86.7%]), followed by functional gastrointestinal disorders including irritable bowel syndrome (21% [95%CI, 13-30%, I25 81.7%]) and RCD1 (10% [95%CI, 0-33%, I25 96.4%]). RCD2 along with its premalignant and malignant sequelae was noted in 8% (95%CI, 2-18%, I25 90.4%) of patients with NRCD. Other causes of NRCD in this review were small intestinal bacterial overgrowth, microscopic colitis, disaccharide intolerance, and inflammatory bowel disease. Conclusion: One in 5 patients with CeD may not respond to GFD and would likely be classified as NRCD. Amongst many other causes, the commonest cause of NRCD was found to be inadvertent exposure to dietary gluten. In order to mitigate NRCD, patients with CeD should receive comprehensive counselling regarding GFD and a systematic approach should be followed for the appropriate evaluation for other causes of NRCD.





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American College of Gastroenterology Annual Scientific Meeting, October 20-25, 2023, Vancouver, Canada